[Treatment reality of esophageal cancer in the Federal State of Brandenburg : Comparison between squamous cell carcinoma and adenocarcinoma]. / Versorgungsrealität des Ösophaguskarzinoms im Bundesland Brandenburg : Ein Vergleich zwischen Plattenepithel- und Adenokarzinomen.

BACKGROUND: Clinical cancer registries are intended to reflect the reality of care through differentiated data analysis and, if necessary, to offer approaches for improving care. METHODS: For the years 2000-2018, the data of the Clinical Epidemiological Cancer Registry Brandenburg-Berlin were examined separately for adenocarcinoma and squamous cell carcinoma with respect to epidemiology and health care reality. RESULTS: Between 2000 and 2018 a total of 3207 esophageal cancers were documented in the cancer registry, of which 2182 were squamous cell carcinomas (ESCC), 843 adenocarcinomas (EAC) and 182 various others or missing histology. During the observation period there was a clear dominance of ESCC but with a significant increase in EAC in both sexes. Overall, the rate of new cases was 5 times higher for men than for women. The relative 5­year survival probability of all esophageal cancers was 17.4% in men and 22.5% in women. Patients with EAC survived significantly longer than those with ESCC. Radiotherapy and chemotherapy, individually or in combination, were mainly used as treatment methods. Surgery was performed on 19% of ESCC and 42% of EAC. CONCLUSION: The proportion of ESCC in Brandenburg is still significantly higher than EAC, with a significant increase for the latter, especially in men. Although locally advanced tumors have been significantly more common, modern neoadjuvant concepts have rarely been documented, and although the quality of the surgery is comparable to the international standard, surgery is carried out in relatively few patients.

Correlation between Obesity and Socioeconomic and Psychological Characteristics of Students Attending Different Rural School Types.

We examined the prevalence of obesity in two types of schools-a comprehensive school and a grammar school-in a rural German region of Brandenburg. METHODS: In a cross-sectional study, BMI values were measured in 114 students in grades 5, 7, and 10. In addition to the demographic data, data on nutrition, physical activity, and mental well-being were collected using a questionnaire. RESULTS: A total of 44% (11/25) of the comprehensive school students and 15% (13/89) of the high school students are overweight, and 24% (6/25) of the comprehensive school pupils and 6% (5/89) of the grammar school pupils (p = 0.009) are obese. In addition, 91% (10/11) of the students with obesity, 36% (4/11) of the students with pre-obesity, and 31% (26/84) of the normal-weight students (p = 0.001) are concerned about their weight. Among the children with obesity, 82% (9/11) are afraid of gaining weight. In addition, 6% (5/82) of the normal-weight students, 25% (3/12) of the students with pre-obesity, and 70% (7/10) of the students with obesity feel restricted by their weight when exercising. CONCLUSION: School attendance and parental socioeconomic status appear to correlate with students' weight statuses. There is a high level of suffering, and they feel uncomfortable with their bodies and worry about weight regulation.

Estimation of central blood pressure waveform from femoral blood pressure waveform by blind sources separation.

Background: Central blood pressure (cBP) is a better indicator of cardiovascular morbidity and mortality than peripheral BP (pBP). However, direct cBP measurement requires invasive techniques and indirect cBP measurement is based on rigid and empirical transfer functions applied to pBP. Thus, development of a personalized and well-validated method for non-invasive derivation of cBP from pBP is necessary to facilitate the clinical routine. The purpose of the present study was to develop a novel blind source separation tool to separate a single recording of pBP into their pressure waveforms composing its dynamics, to identify the compounds that lead to pressure waveform distortion at the periphery, and to estimate the cBP. The approach is patient-specific and extracts the underlying blind pressure waveforms in pBP without additional brachial cuff calibration or any a priori assumption on the arterial model. Methods: The intra-arterial femoral BPfe and intra-aortic pressure BPao were anonymized digital recordings from previous routine cardiac catheterizations of eight patients at the German Heart Centre Berlin. The underlying pressure waveforms in BPfe were extracted by the single-channel independent component analysis (SCICA). The accuracy of the SCICA model to estimate the whole cBP waveform was evaluated by the mean absolute error (MAE), the root mean square error (RMSE), the relative RMSE (RRMSE), and the intraclass correlation coefficient (ICC). The agreement between the intra-aortic and estimated parameters including systolic (SBP), diastolic (DBP), mean arterial pressure (MAP), and pulse pressure (PP) was evaluated by the regression and Bland-Altman analyses. Results: The SCICA tool estimated the cBP waveform non-invasively from the intra-arterial BPfe with an MAE of 0.159 ± 1.629, an RMSE of 5.153 ± 0.957 mmHg, an RRMSE of 5.424 ± 1.304%, and an ICC of 0.94, as well as two waveforms contributing to morphological distortion at the femoral artery. The regression analysis showed a strong linear trend between the estimated and intra-aortic SBP, DBP, MAP, and PP with high coefficient of determination R2 of 0.98, 0.99, 0.99, and 0.97 respectively. The Bland-Altman plots demonstrated good agreement between estimated and intra-aortic parameters with a mean error and a standard deviation of difference of -0.54 ± 2.42 mmHg [95% confidence interval (CI): -5.28 to 4.20] for SBP, -1.97 ± 1.62 mmHg (95% CI: -5.14 to 1.20) for DBP, -1.49 ± 1.40 mmHg (95% CI: -4.25 to 1.26) for MAP, and 1.43 ± 2.79 mmHg (95% CI: -4.03 to 6.90) for PP. Conclusions: The SCICA approach is a powerful tool that identifies sources contributing to morphological distortion at peripheral arteries and estimates cBP.

Downsizing of rectal cancer following neoadjuvant radiotherapy (5 × 5 Gy) and long interval surgery evaluated using MRI semiautomated volumetric measurements, a retrospective study.

Introduction: Neoadjuvant conventional chemoradiation (CRT) is the standard treatment for primary locally non-curatively resectable rectal cancer, as tumor downsizing may allow R0 resectability. Short-term neoadjuvant radiotherapy (5x5 Gy) followed by an interval before surgery (SRT- delay) is an alternative for multimorbid patients who cannot tolerate CRT. This study examined the extent of tumor downsizing achieved with the SRT-delay approach in a limited cohort that underwent complete re-staging before surgery. Methods: Between March 2018 and July 2021, 26 patients with locally advanced primary adenocarcinoma (>uT3 or/and N+) of the rectum were treated with SRT-delay. 22 patients underwent initial staging and complete re-staging (CT, endoscopy, MRI). Tumor downsizing was assessed by staging and re-staging data and pathologic findings. Semiautomated measurement of tumor volume was performed using mint Lesion™ 1.8 software to evaluate tumor regression. Results: The mean tumor diameter determined on sagittal T2 MRI images decreased significantly from 54.1 (23-78) mm at initial staging to 37.9 (18-65) mm at re-staging before surgery (p <0.001) and to 25.5 (7-58) mm at pathologic examination (p <0.001). This corresponds to a mean reduction in tumor diameter of 28.9 (4.3-60.7) % at re-staging and 51.1 (8.7-86.5) % at pathology. Mean tumor volume determined from transverse T2 MR images mint LesionTM 1.8 software significantly decreased from 27.5 (9.8 - 89.6) cm3 at initial staging to 13.1 (3.7 - 32.8) cm3 at re-staging (p <0.001), corresponding to a mean reduction of 50.8 (21.6 - 77) %. The frequency of positive circumferential resection margin (CRM) (less than 1mm) decreased from 45,5 % (10 patients) at initial staging to 18,2 % (4 patients) at re-staging. On pathologic examination, the CRM was negative in all cases. However, multivisceral resection for T4 tumors was required in 2 patients (9%). Tumor downstaging was noted in 15 of 22 patients after SRT-delay. Conclusion: In conclusion, the observed extent of downsizing is broadly comparable to the results of CRT, making SRT-delay a serious alternative for patients who cannot tolerate chemotherapy.

Generation of colon cancer-derived tumor-infiltrating T cells (TILs) for adoptive cell therapy.

Adoptive cell therapy (ACT) using specific immune cells and stem cells has emerged as a promising treatment option that could complement traditional cancer therapies in the future. In particular, tumor-infiltrating lymphocytes (TILs) have been shown to be effective against solid tumors in various clinical trials. Despite the enormous disease burden and large number of premature deaths caused by colorectal cancer (CRC), studies on TILs isolated from tumor tissue of patients with CRC are still rare. To date, studies on ACT often lack controlled and comparable expansion processes as well as selected ACT-relevant T-cell populations. We describe a procedure for generating patient-specific TILs, which are prerequisites for clinical trials of ACT in CRC. The manufacturing and characteristics of these TILs differ in important modalities from TILs commonly used for this therapeutic approach. Tumor tissue samples were obtained from 12 patients undergoing surgery for primary CRC, predominantly with low microsatellite instability (pMMR-MSI-L). Tumors in the resected specimens were examined pathologically, and an approved volume of tumor tissue was transferred to a disposable perfusion bioreactor. Tissue samples were subjected to an automatically controlled and highly reproducible cultivation process in a GMP-conform, closed perfusion bioreactor system using starting medium containing interleukin-2 and interleukin-12. Outgrowth of TIL from tissue samples was initiated by short-term supplementation with a specific activation cocktail. During subsequent expansion, TILs were grown in interleukin-2-enriched medium. Expansion of TILs in a low-scaled, two-phase process in the Zellwerk ZRP bioreactor under hyperoxic conditions resulted in a number of approximately 2 × 109 cells. The expanded TILs consisted mainly (73%) of the ACT-relevant CD3+/CD8+ effector memory phenotype (CD45RO+/CCR7-). TILs harvested under these conditions exhibited high functional potential, which was confirmed upon nonspecific stimulation (interferon-γ, tumor necrosis factor-α cytokine assay).

Pelvic Intraoperative Neuromonitoring Prevents Dysfunction in Patients With Rectal Cancer: Results From a Multicenter, Randomized, Controlled Clinical Trial of a NEUROmonitoring System (NEUROS).

OBJECTIVE: This NEUROmonitoring System (NEUROS) trial assessed whether pelvic intraoperative neuromonitoring (pIONM) could improve urogenital and ano-(neo-)rectal functional outcomes in patients who underwent total mesorectal excisions (TMEs) for rectal cancer. BACKGROUND: High-level evidence from clinical trials is required to clarify the benefits of pIONM. METHODS: NEUROS was a 2-arm, randomized, controlled, multicenter clinical trial that included 189 patients with rectal cancer who underwent TMEs at 8 centers, from February 2013 to January 2017. TMEs were performed with pIONM (n=90) or without it (control, n=99). The groups were stratified according to neoadjuvant chemoradiotherapy and sex, with blocks of variable length. Data were analyzed according to a modified intention-to-treat protocol. The primary endpoint was a urinary function at 12 months after surgery, assessed with the International Prostate Symptom Score, a patient-reported outcome measure. Deterioration was defined as an increase of at least 5 points from the preoperative score. Secondary endpoints were sexual and anorectal functional outcomes, safety, and TME quality. RESULTS: The intention-to-treat analysis included 171 patients. Marked urinary deterioration occurred in 22/171 (13%) patients, with significantly different incidence between groups (pIONM: n=6/82, 8%; control: n=16/89, 19%; 95% confidence interval, 12.4-94.4; P =0.0382). pIONM was associated with better sexual and ano-(neo)rectal function. At least 1 serious adverse event occurred in 36/88 (41%) in the pIONM group and 53/99 (54%) in the control group, none associated with the study treatment. The groups had similar TME quality, surgery times, intraoperative complication incidence, and postoperative mortality. CONCLUSION: pIONM is safe and has the potential to improve functional outcomes in rectal cancer patients undergoing TME.

[Reality of care of colorectal cancer in the State of Brandenburg : With special consideration of the number of hospital cases and certification as a colorectal cancer center]. / Die Versorgungsrealität des kolorektalen Karzinoms im Bundesland Brandenburg : Unter besonderer Berücksichtigung der Krankenhausfallzahlen und Zertifizierung als Darmkrebszentrum.

Analysis of the quality of care for colorectal cancer is an essential foundation for further development and is based on the comparison of the goals set and the actual quality of care. This publication presents the reality of care in the State of Brandenburg covering the complete spectrum of treating clinics based on the data of the clinical cancer register. This study analyzed the number of resected and examined lymph nodes, the quality of total mesorectal excision (TME), the residual tumor (R0) resection rate and the proportion of adjuvant therapy of colon cancer in Union internationale contre le cancer (UICC) stage III depending on the operation quota of hospitals and the certification as bowel cancer center according to Onkozert. Apart from the R status, the analyses showed no differences in the qualitative operation data from the clinical cancer register depending on the hospital volume.

Laparoscopic vs. Open Surgical Repair of Subxiphoidal Hernia Following Median Sternotomy for Coronary Bypass - Analysis of the Herniamed Registry.

Introduction: The repair of subxiphoidal incisional hernia following median sternotomy is technically demanding due to the specific anatomic situation and the lateral distracting forces in this region. Published data are available from retrospective reports with limited number of patients only. The aim of this study was to evaluate the outcome of subxiphoidal hernia repair comparing laparoscopic and open surgical approach. Materials and Methods: This analysis of Herniamed registry data of patients with subxiphoidal incisional hernia following sternotomy for coronary bypass assesses the perioperative and 1 year follow-up outcome of laparoscopic and open repair. Demographic data and perioperative outcomes were stratified by surgical approach (laparoscopic vs. open) and compared as unadjusted analyses using Chi square and Students t-tests. Results: Of 208 patients identified for the analysis 69 patients (33.2%) underwent laparoscopic and 139 (66.8%) patients had open repair. Concerning demographic data (gender, age, BMI, ASA score), risk factors and hernia size there were no significant differences between laparoscopic and open repair group. For intraoperative, postoperative and general complications as well as complication related re-operations no significant differences were seen between the groups. No significant advantage could be stated for laparoscopic repair regarding duration of operation and hospital stay. The recurrence rate at 1 year follow-up was higher in the laparoscopic group (7.2 vs. 2.2%; p = 0.072). No significant differences were reported in the 1 year follow-up evaluation of pain at rest, pain on exertion and pain requiring treatment. Conclusion: The repair of subxiphoidal incisional hernia is safe in both open and laparoscopic technique. With regard to the lower recurrence rate preference can be given to open repair.

Nonocclusive mesenteric ischemia associated with postoperative jejunal tube feeding: Indicators for clinical management.

Postoperative nutrition via a jejunal tube after major abdominal surgery is usually well tolerated. However, some patients develop nonocclusive mesenteric ischemia (NOMI). This morbid complication has a grave prognosis with a mortality rate of 41% to 100%. Early symptoms are nonspecific, and no treatment guideline is available. We reviewed cases of NOMI at our institution and cases described in the literature to identify factors that impact the clinical course. Among five patients, three had no necrosis and one had segmental necrosis and perforation. These patients recovered with limited resection and decompression of the bowel and abdominal compartment. In one patient with extended bowel necrosis at the time of re-laparotomy, NOMI progressed and the patient died of multiple organ failure. The extent of small bowel necrosis at the time of re-laparotomy is a relevant prognostic factor. Therefore, early diagnosis and treatment of NOMI can improve the prognosis. Clinical symptoms of abdominal distension, cramps and high reflux plus paraclinical signs of leukocytosis, hypotension and computed tomography findings of a distended small bowel with pneumatosis intestinalis and portal venous gas can help to establish the diagnosis. We herein introduce an algorithm for the diagnosis and management of NOMI associated with jejunal tube feeding.

Negative Pressure Wound Therapy vs Conventional Wound Treatment in Subcutaneous Abdominal Wound Healing Impairment: The SAWHI Randomized Clinical Trial.

Importance: Negative pressure wound therapy (NPWT) is an established treatment option, but there is no evidence of benefit for subcutaneous abdominal wound healing impairment (SAWHI). Objective: To evaluate the effectiveness and safety of NPWT for SAWHI after surgery in clinical practice. Design, Setting, and Participants: The multicenter, multinational, observer-blinded, randomized clinical SAWHI study enrolled patients between August 2, 2011, and January 31, 2018. The last follow-up date was June 11, 2018. The trial included 34 abdominal surgical departments of hospitals in Germany, Belgium, and the Netherlands, and 539 consecutive, compliant adult patients with SAWHI after surgery without fascia dehiscence were randomly assigned to the treatment arms in a 1:1 ratio stratified by study site and wound size using a centralized web-based tool. A total of 507 study participants (NPWT, 256; CWT, 251) were assessed for the primary end point in the modified intention-to-treat (ITT) population. Interventions: Negative pressure wound therapy and conventional wound treatment (CWT). Main Outcomes and Measures: The primary outcome was time until wound closure (delayed primary closure or by secondary intention) within 42 days. Safety analysis comprised the adverse events (AEs). Secondary outcomes included wound closure rate, quality of life (SF-36), pain, and patient satisfaction. Results: Of the 507 study participants included in the modified ITT population, 287 were men (56.6%) (NPWT, 155 [60.5%] and CWT, 132 [52.6%]) and 220 were women (43.4%) (NPWT, 101 [39.5%] and CWT 119 [47.4%]). The median (IQR) age of the participants was 66 (18) years in the NPWT arm and 66 (20) years in the CWT arm. Mean time to wound closure was significantly shorter in the NPWT arm (36.1 days) than in the CWT arm (39.1 days) (difference, 3.0 days; 95% CI 1.6-4.4; P < .001). Wound closure rate within 42 days was significantly higher with NPWT (35.9%) than with CWT (21.5%) (difference, 14.4%; 95% CI, 6.6%-22.2%; P < .001). In the therapy-compliant population, excluding study participants with unauthorized treatment changes (NPWT, 22; CWT, 50), the risk for wound-related AEs was higher in the NPWT arm (risk ratio, 1.51; 95% CI, 0.99-2.35). Conclusions and Relevance: Negative pressure wound therapy is an effective treatment option for SAWHI after surgery; however, it causes more wound-related AEs. Trial Registration: ClinicalTrials.gov Identifier: NCT01528033.

Bilateral giant inguinoscrotal hernia. Presentation of a novel combined two-stage repair approach.

Giant inguinoscrotal hernia is typically defined as hernia extending below the midpoint of the inner thigh, in the standing position. These hernias can be a demanding surgical problem as replacing bowel contents into the abdomen that can cause a life-threatening increase in intra-abdominal pressures. Various techniques such as preoperative progressive pneumoperitoneum (PPP), debulking of abdominal contents with visceral resections with or without omentectomy and phrenectomy have been suggested. We report the case of a 65-year-old patient with giant bilateral inguinal hernia. We applied a novel two-stage combined approach consisting of PPP with simultaneous single shot injection of botulinum toxin Type A into the anterior abdominal wall, and a second stage laparotomy with hernia repair (Stoppa technique). This technique makes possible the successful treatment of giant inguinal hernias without the need for visceral resection. To our knowledge, this is the first presented case of this combined treatment modality.

THBS4, a novel stromal molecule of diffuse-type gastric adenocarcinomas, identified by transcriptome-wide expression profiling.

Gastric adenocarcinomas can be divided into two major histological types, the diffuse and intestinal type (Laurén classification). Since they diverge in many clinical and molecular characteristics, it is widely accepted that they represent distinct disease entities that may benefit from different therapeutic approaches. Gene expression profiling studies have identified numerous genes that are differentially expressed between them. However, none of these studies covered the whole transcriptome and the published gene lists reveal little overlap, raising the need for further, more comprehensive analyses. Here, we present the first transcriptome-wide expression profiling study comparing the two types (diffuse n=19, intestinal n=24), which identified >1000 genes that are differentially expressed. Among them, thrombospondin 4 (THBS4) showed the strongest correlation to histological type, with vast overexpression in the diffuse type. Quantitative real-time PCR validated this strong overexpression and revealed that intestinal tumors generally lack THBS4 expression. Immunohistochemistry demonstrated THBS4 overexpression on the protein level (n=10) and localized THBS4 to the stromal aspect. Its expression was primarily observed within the extracellular matrix surrounding the tumor cells, with the highest intensities found in regions of high tumor cell density and invasion. Intestinal tumors and matched non-neoplastic gastric epithelium and stroma did not feature any relevant THBS4 expression in a preliminary selection of analyzed cases (n=5). Immunohistochemical colocalization and in vitro studies revealed that THBS4 is expressed and secreted by cancer-associated fibroblasts. Furthermore, we show that THBS4 transcription in fibroblasts is stimulated by tumor cells. This study is the first to identify THBS4 as a powerful marker for diffuse-type gastric adenocarcinomas and to provide an initial characterization of its expression in the course of this disease.

Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954.

PURPOSE: Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines. PATIENTS AND METHODS: Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required. RESULTS: This trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466). CONCLUSION: This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).

Current status of sentinel lymph node biopsy in adenocarcinoma of the distal esophagus, gastric cardia, and proximal stomach.

The resection of the adenocarcinoma of the esophagogastric junction should be considered to the extent of the lymphatic drainage. This, on the other hand, depends on the possible lymphatic metastasizing. As an adenocarcinoma of the esophagogastric junction is located along the borderline between two visceral cavities (mediastinal/abdominal), it can, in principle, metastasize in both cavities. There is not, however, an imaging (CT, MRI, PET) that can adequately assure the detection of a beginning lymph node metastasis in particular. The sentinel lymph node biopsy could provide the beginning of a solution in this case. The initial results, with all of the necessary accompanying technical work, have been encouraging. The paper presented here provides an introduction to the challenge of the SLNB and the background of a specialized surgical therapy of the AEG. If a lymph nodal metastasis can be definitely confirmed or ruled out, many patients could be spared an unnecessary lymphadenectomy. This is especially important at the AEG because minimizing the evasiveness of the surgery with adequate radical oncological resection (e.g., without thoracotomy) would mean a substantial reduction of postoperative mortality.

Perineal colostomy with spiral smooth muscle graft for neosphincter reconstruction following abdominoperineal resection of very low rectal cancer: long-term outcome.

BACKGROUND: To avoid abdominal colostomy and improve quality of life, several types of anorectal reconstruction following abdominoperineal resection have been proposed. The aim of this study was to assess functional results and the quality of life of patients with very low rectal cancer after abdominoperineal resection and neosphincter reconstruction by perineal colostomy with a colonic muscular cuff. PATIENTS AND METHODS: Twenty-seven patients who had undergone neosphincter reconstruction with a perineal spiral cuff plasty after abdominoperineal resection were included in a retrospective study to evaluate long-term outcome. The functional results were analyzed using anal manometry and the continence score. The quality of life was measured with the global and disease-specific questionnaires European Organization for Research and Treatment of Cancer QLQ-C30 and C38. RESULTS: Median follow-up time was 105 months (range, 18-185 mo). The median Holschneider continence score of the study sample was 13 (continent), with a range of 10 (partially continent) to 16 (continent), thus demonstrating satisfactory functional results. The functional assessment was completed by neosphincter manometry which revealed a median resting vs compression pressure of 40 vs 96 cmH2O with a range of 5 to 81 cmH2O vs 49 to 364 cmH2O. The quality-of-life analyses showed an above-average score for both global health and disease-specific status. CONCLUSION: Spiral cuff colostomy with reconstruction after abdominoperineal resection of very low distal rectal cancer offers a surgical option for a selective group of patients with reasonable functional long-term results and an improved quality of life.

Technique and clinical consequences of sentinel lymph node biopsy in colorectal cancer.

Sentinel lymph node biopsy (SLNB) in colorectal cancer (CRC) is a controversial issue. Different detection techniques, various protocols for the histopathological work-up of the SLN and a greatly differing experience between the investigators make the comparison of the available studies problematic. Nevertheless, it is clear, that the successful clinical application of SLNB in breast cancer and melanoma cannot simply be transferred into colorectal cancer treatment. In this paper we try to define the current status of clinical application of this technique in CRC by means of a literature review and our own experience. Moreover, the background and the potential clinical implications of additionally small tumor deposits in the SLN (so-called "upstaging") is critically reviewed. Summarizing the results, it is clear, that the value of SLNB in CRC is still unclear. If current techniques are to be applied outside a study protocol and no patient selection is performed the correct identification of macrometastases needs further investigation. Although still under debate, there is otherwise growing evidence, that -at least if RT-PCR-techniques are used- the detection of small tumor deposits in the SLN may be of prognostic and therefore clinical value. Future studies should focus on two subjects: First, alternative detection techniques and careful patient selection may clarify, if an improvement of the sensitivity to detect macrometastases is feasible. Second, large prospective trials using a standardized histopathological lymph node assessment should compare SLN and Non-SLN for its incidence to bear small tumor deposits. If SLNB proves to be sensitive, the prognostic and predictive value of these additional findings should be clarified.

Sentinel lymph node biopsy in colon cancer: a prospective multicenter trial.

INTRODUCTION: The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results. METHODS: Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor. The SLN underwent step sections and immunohistochemistry (IHC), if classified free of metastases after routine hematoxylin and eosin examination. RESULTS: At least one SLN (median, n = 2) was identified in 268 of 315 enrolled patients (detection rate, 85%). Center experience, lymphovascular invasion, body mass index (BMI), and learning curve were positively associated with the detection rate. The false-negative rate to identify pN+ patients by SLNB was 46% (38 of 82). BMI showed a significant association to the false-negative rate (P < 0.0001), the number of tumor-involved lymph nodes was inversely associated. If only slim patients (BMI < or =24) were investigated in experienced centers (>22 patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21% (30 of 141) of the patients, classified as pN0 by routine histopathology, revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN. CONCLUSIONS: The contribution of SLNB to conventional nodal staging of colon cancer patients is still unspecified. Technical problems have to be resolved before a definite conclusion can be drawn in this regard. However, SLNB identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes. Further studies must clarify the clinical impact of these findings in terms of prognosis and the indication of adjuvant therapy.

Efficacy of different technical procedures for sentinel lymph node biopsy in gastric cancer staging.

BACKGROUND: The clinical impact of sentinel lymph node biopsy (SLNB) in gastric cancer is controversial. We performed a prospective trial to compare different methods: radiocolloid method (RM), dye method (DM), and both methods simultaneously (dual method, or DUM) for reliability and therapeutic consequences. METHODS: RM and DM were applied in 35 gastric cancer patients. After endoscopic peritumoral injection of (99m)Tc-colloid and Patent Blue V, the positions of all blue sentinel lymph nodes (SLNs) were recorded, and the SLNs microscopically examined by hematoxylin and eosin, step sections, and immunohistochemistry. RESULTS: RM, DM, and DUM identified the SLNs in 34 (97%) of 35 patients. The sensitivity for the prediction of positive lymph node status for RM was 22 (92%) of 24, for DM 16 (66%) of 24, and for DUM 22 (92%) of 24. In 7 of 17 (RM), 5 of 15 (DM), and 7 of 17 (DUM) patients classified as N0 by routine hematoxylin and eosin staining, micrometastases or isolated tumor cells were found in the SLN (upstaging) after focused examination. If only a limited lymph node dissection of the SLN basins would have been performed in patients, residual lymph node metastases were left in 9 of 24 (RM), in 7 of 34 (DM), and in 5 of 24 (DUM) of patients with node-positive disease. CONCLUSIONS: Use of RM was superior. DUM did not further increase the sensitivity. A limited lymph node dissection-i.e., lymphatic basin in patients with SLN-positive disease-is associated with a high risk of residual metastases. Patients with negative SLNs may be selected for a limited surgical procedure if they meet certain criteria.

Prognostic value of cytokeratin-positive bone marrow cells of gastric cancer patients.

BACKGROUND: Epithelial cells in the bone marrow of patients with gastric cancer suggest tumor dissemination; however, their prognostic implications are controversial. We prospectively evaluated the correlation of bone marrow findings, recurrence rate, and disease-free survival after long-term follow-up. METHODS: Bone marrow were aspirated from both iliac crests and stained with monoclonal cytokeratin (CK)-18 antibody in 209 patients before their initial operation. Patients were followed up for a median of 56 months. RESULTS: Overall, 39 (19%) of 209 patients and 15 (14%) of 109 R0-resected patients had CK-positive cells. CK-positive patients had more local, regional, and distant recurrence than CK-negative patients (P < .05). We found a significantly shorter disease-free survival (P < .05) in the patients with >2 CK-positive cells per 2 x 10(6) bone marrow cells (mean, 35 months) than in patients with 2 CK-positive cells per 2 x 10(6) bone marrow cells was an independent prognostic factor for tumor-related death (P < .05). CONCLUSIONS: Not only the mere presence of CK-positive epithelial cells in bone marrow, but also the cell number, correlates with prognosis. Our findings suggest that classifying CK-positive bone marrow cells in these patients will facilitate future studies.

Vascular endothelial growth factor-D and its receptor VEGFR-3: two novel independent prognostic markers in gastric adenocarcinoma.

PURPOSE: Vascular endothelial growth factor (VEGF)-D and its homolog VEGF-C influence lymphangiogenesis through activation of VEGF receptor 3 (VEGFR-3), and have been implicated in lymphatic tumor spread. Nodal dissemination of gastric adenocarcinomas critically determines clinical outcome and therapeutic options of affected patients. Therefore, we analyzed expression and prognostic significance of VEGF-D along with VEGF-C, and VEGFR-3 in gastric adenocarcinomas. MATERIALS AND METHODS: VEGF-C, VEGF-D, and VEGFR-3 were analyzed in 91 R(0)-resected primary gastric adenocarcinomas, corresponding noncancerous gastric mucosa, and lymph node metastases employing immunohistochemistry and/or in situ hybridization. Blood and lymph vessel densities were assessed after staining with CD31 and LYVE-1-specific antibodies. RESULTS: VEGF-D and VEGF-C were detected in 67.0% and 50.5% of gastric cancers, respectively. Healthy gastric mucosa was negative for VEGF-C and in 12.5% positive for VEGF-D. Presence of VEGF-D (P = .005) or VEGF-C (P = .006) was correlated with lymphatic metastases and decreased survival (VEGF-D, P < .05; VEGF-C, P < .05). VEGFR-3 was correlated with reduced carcinoma-specific survival (P < .05), and Cox multivariate regression analysis qualified VEGF-D and VEGFR-3, but not VEGF-C, as independent prognostic parameters. In lymph node-positive gastric cancers, presence of VEGF-D/VEGFR-3 was associated with poor survival, whereas absence of VEGF-D/VEGFR-3 defined a subgroup of patients with clearly favorable prognosis. CONCLUSION: VEGF-D and VEGFR-3 are novel independent prognostic marker molecules aiding to identify patients with poor prognosis after curative resection of gastric adenocarcinomas. Combined analysis of the VEGF-C/VEGF-D/VEGFR-3 system can be useful to identify patients with unfavorable clinical outcome and thereby may help to refine therapeutic decisions in gastric cancer.